Increase In Respiratory Frequency Research Articles

EFEKTIFITAS TEKNIK PERNAPASAN BUTEYKO UNTUK MENINGKATKAN PENGONTROLAN ASMA BRONKIAL DI PUSKESMAS KOTA PADANG

ABSTRACT
 Bronchial asthma is one of the chronic respiratory diseases caused by the narrowing of the airways due to hypersensitivity reactions in the bronchi, resulting in symptoms such as wheezing, coughing, and shortness of breath. When asthma patients experience breathlessness, there is an increase in respiratory frequency and a decrease in oxygen saturation. If not promptly treated, it can lead to oxygen deficiency (hypoxia), which can ultimately result in death. The management of bronchial asthma is typically done with pharmacological therapy aimed at achieving a normal lifestyle, avoiding attacks, and restoring optimal lung function. However, it has not shown significant improvement in preventing bronchial asthma. Non-pharmacological treatment methods, such as Buteyko breathing technique, are expected to complement pharmacological treatment in reducing the frequency of asthma attacks (exacerbations). The Buteyko breathing technique has shown an increase in peak expiratory flow rate (PEFR) values and a decrease in bronchial asthma score values. The objective of this study is to analyze the effectiveness of the Buteyko breathing technique in controlling bronchial asthma in the Padang Health Center area. Before the intervention, the average bronchial asthma control was 15.44, with a standard deviation of 2.279, and a minimum control of 11 and a maximum of 19. After the intervention, the average control increased to 21.69, with a standard deviation of 2.387, and a minimum control of 16 and a maximum of 25. Similarly, bronchial asthma control in the control group showed an increase from 16.19 to 15.38 after the intervention. Statistical tests using independent t-tests showed a significant influence of the Buteyko breathing technique on bronchial asthma control, with a p-value of 0.000 (p?0.05). This indicates that the Buteyko breathing technique has a significant impact on improving bronchial asthma control. Therefore, this research provides evidence that the Buteyko breathing technique can be a valuable addition to the treatment of bronchial asthma, helping patients achieve better control of their condition and reducing the risk of asthma attacks.
 Keywords: Buteyko breathing technique; Breathing patterns.

High variation in the response of calves to a low-dose lipopolysaccharide challenge is associated with early-life measurements

Lipopolysaccharide (LPS) challenges are commonly used in animal studies as a model for infection with gram-negative bacteria and innate immune activation. We used a low-dose LPS challenge for evaluating interindividual variation in innate immune responses in calves. This was part of a larger study aimed at predicting interindividual variation in feed efficiency in veal calves by variation in feeding motivation, digestion, metabolism, immunology, and behavioral traits. However, due to unexpected high mortality, this LPS challenge was performed in 32 calves rather than in 130 calves, which was initially intended in that larger study, and the 32 calves subjected to the LPS challenge were removed from that larger study. The objective of this short communication is to report the effects of a low-dose LPS challenge in those 32 calves and to examine whether the high variation in calves' responses to LPS could be explained by parameters related to feeding motivation, digestion, behavior, and immunology measured in early life. Thirty-two male Holstein-Friesian calves of Dutch origin were intravenously injected with LPS (0.05 μg/kg of body weight) at an age of 72 ± 0.6 d. Rectal temperature and respiratory frequency were recorded before injection and every hour after injection up to 6 h. In the 8 wk before the LPS challenge, measurements were performed related to general health, feeding motivation, digestion, behavior, and immunity. Following LPS administration, 3 calves died of shock, a fourth calf was euthanized because of severe symptoms of shock and 3 other calves were treated with corticosteroids to counteract observed symptoms of shock. Within the group of 25 relatively mild-responding calves, large interindividual variation in clinical responses to LPS was observed. The maximum increase in rectal temperature varied from 0.6 to 1.9°C and averaged 1.2 ± 0.39°C (coefficient of variation was 32%). The maximum increase in respiratory frequency varied from 16 to 132 bouts/min and averaged 60 ± 28 bouts/min (coefficient of variation was 48%). Little differences were found in early-life measurements between the 7 heavy and 25 mild responders, although heavy responders tended to have a better umbilical hernia score, and had a lower score in a human approach test (i.e., were less reactive) and lower presence of fecal pathogens. The maximum increase in rectal temperature correlated negatively with blood hemoglobin concentration at arrival of the calves at the facilities (r = −0.59) and in wk 4 (r = −0.53). The maximum increase in respiratory frequency correlated negatively with fecal color score (r = −0.43) and positively with fur score in wk 5 (r = 0.50). Overall, mortality (12.5%) and variation in clinical response was high after a low-dose LPS challenge in clinically healthy calves and some hematological and health measurements in early life were related to the clinical response of calves to LPS.

Upregulation of breathing rate during running exercise by central locomotor circuits in mice

While respiratory adaptation to exercise is compulsory to cope with the increased metabolic demand, the neural signals at stake remain poorly identified. Using neural circuit tracing and activity interference strategies in mice, we uncover here two systems by which the central locomotor network can enable respiratory augmentation in relation to running activity. One originates in the mesencephalic locomotor region (MLR), a conserved locomotor controller. Through direct projections onto the neurons of the preBötzinger complex that generate the inspiratory rhythm, the MLR can trigger a moderate increase of respiratory frequency, prior to, or even in the absence of, locomotion. The other is the lumbar enlargement of the spinal cord containing the hindlimb motor circuits. When activated, and through projections onto the retrotrapezoid nucleus (RTN), it also potently upregulates breathing rate. On top of identifying critical underpinnings for respiratory hyperpnea, these data also expand the functional implication of cell types and pathways that are typically regarded as “locomotor” or “respiratory” related.

Impact of the glutamatergic neurotransmission within the A5 region on the cardiorespiratory response evoked from the midbrain dlPAG

Stimulation of the dorsolateral periaqueductal grey matter (dlPAG) in rats evokes an active defensive behaviour together with a cardiorespiratory response characterised by tachypnoea, tachycardia and hypertension. The dlPAG neurons involved in these responses are excitatory, presumably glutamatergic, due to the presence of vesicular glutamate transporter VGLUT2 within their axon terminals. Previously, our group described a functional interaction between dlPAG and the pontine A5 region. Accordingly, in the present work, in order to characterize the role of glutamate within this interaction, experiments were carried out in spontaneously breathing anaesthetized rats (sodium pentobarbitone 60 mg/kg i.p., suplemented with 20 mg/kg i.p.). The cardiorespiratory response evoked by electrical stimulation of the dlPAG (1 ms pulses, 20–50 μA, given at 100 Hz, during 5 s) was analysed before and after the microinjection, within the A5 region, of either kynurenic acid (non-specific glutamate receptor antagonist; 5–10 nmol), DAP-5 (NMDA antagonist; 1 pmol), CNQX (non-NMDA antagonist; 1 pmol) or MCPG (metabotropic antagonist; 0,1 nmol). Kynurenic acid decreased the intensity of both the tachypnoea (p < 0,001) and tachycardia (p < 0,001) induced by dl-PAG stimulation. Blockade of no-NMDA receptors reduced the increase of respiratory frequency, heart rate and pressor response to dl-PAG stimulation (p < 0,01, p < 0,001, p < 0,05 respectively). Blockade of either NMDA or metabotropic receptors reduced the dlPAG-evoked tachycardia and pressor response (p < 0,01; p < 0,05 respectively). These results suggest a neuromodulatory role for A5 region via glutamate neurotransmission of the dlPAG-evoked cardiorespiratory response, confirming the role of the ventrolateral pons in the neuronal circuits involved in respiratory and heart rate control.

Investigation on forced vibration characteristics of Nitinol tracheal stent.

Tracheal stents can be placed in a narrow position in the human trachea to ensure smooth breathing. And the stent will deform during service by the influence of the physiological environment or random excitations, such as coughing. This paper divides the vibration into periodic and random vibrations according to the different pressures. And a coupling vibration model was established by analyzing the contact relationship between the stent and the trachea tissue. And this study discusses the influence of tracheal diameter, respiratory pressure, and frequency on the stent vibration characteristics through Ansys simulation. In addition, the nonlinear equations were solved by the Matlab numerical analysis method, which could help analyze the influence of cough intensity on the stability of the tracheal stent system. The results showed that when tracheal stenosis occurred in the trachea's more significant grade, the trachea stent was more likely to fall off when treated with a tracheal stent. With the increase in respiratory frequency and pressure, the deformation of the tracheal stent is more considerable. Moreover, the frequency of normal cough hardly affects the stability of the stent system, while the excitation force and damping coefficient value greatly influence the system. When the excitation force of the cough exceeds the critical importance of 20N, the tracheal stent is prone to fall off. This study comprehensively obtained the forced vibration characteristics of the stent under service conditions, which could make up for the shortage of the vibration theory of the stent. The results can provide a theoretical basis for predicting the possibility of stent loss in clinical treatment.

Long-term heat stress at final gestation: physiological and heat shock responses of Saanen goats.

The long exposure to heat negatively changes performance and productivity of animals, particularly when heat stress is associated with gestation. Indeed, little is known about the negative effects of long-term heat stress on the final gestation of dairy goats. In this context, the physiological and cellular responses of Saanen goats submitted to heat stress (37°C from 10:00 to 16:00 h) were investigated from day 60th pre-partum to day 60th post-partum. At final gestation, 46 pregnant Saanen goats were randomly assigned to the treatments: control (CT; thermal neutral conditions) and heat stress (HS; climatic chamber). After partum, all experimental goats were maintained in thermal neutral conditions. The rectal, dorsal, mammary temperatures and respiratory frequency, cortisol release, milk yield, milk quality, and the genes HSP60, HSP70, HSP90, Glucocorticoid receptor and ACTHR. Goats subjected to HS showed significantly (P < 0.05) higher rectal, dorsal, and mammary temperatures and significantly mobilized the increase of respiratory frequency to lose heat as compared to CT goats. The HS challenge significantly increased cortisol release from day 15th pre-partum to day 15th post-partum. CT goats produced more milk than HS from weeks 4 to 10 of lactation (P <0.001), with no difference in milk quality. However, on day 15th post-partum, there was a significant effect of HS treatment on the expression of HSP70 and ACTHR genes as compared to CT treatment, confirming the long-term effect of HS on Saanen goats. In conclusion, the physiological parameters studied increased pre-partum in the hottest hour, and cortisol peaked on day 15 pre-partum for heat-stressed goats. Although on the 15th day post-partum, all goats were in thermal comfort, and the physiological parameters were within the normal range, the concentration of cortisol continued to be significantly higher for goats submitted to thermal stress. Indeed, milk yield was greater for goats subjected to pre-partum thermal comfort. Furthermore, the expression of HSP70 and ACTHR genes on peripheral blood mononuclear cells are interesting biomarkers for studying the long-term effect of heat stress on Saanen goats.

Neural mechanisms underlying respiratory regulation within the preBötzinger complex of the rabbit

The preBötzinger complex (preBötC) is a medullary area essential for normal breathing and widely recognized as necessary and sufficient to generate the inspiratory phase of respiration. It has been studied mainly in rodents. Here we report the main results of our studies revealing the characteristics of the rabbit preBötC identified by means of neuronal recordings, D,L-homocysteic acid microinjections and histological controls. A crucial role in the respiratory rhythmogenesis within this neural substrate is played by excitatory amino acids, but also GABA and glycine display important contributions. Increases in respiratory frequency are induced by microinjections of neurokinins, somatostatin as well by serotonin (5-HT) through an action on 5-HT1A and 5-HT3 receptors or the disinhibition of a GABAergic circuit. Respiratory depression is observed in response to microinjections of the μ-opioid receptor agonist DAMGO. Our results show similarities and differences with the rodent preBötC and emphasize the importance of comparative studies on the mechanisms underlying respiratory rhythmogenesis in different animal species.

Electrical Stimulation of Afferent Lumbar Sympathetic Nerve Impacts Cardio‐Respiratory Functions in Anesthetized Rats

The lumbar sympathetic chains (LSC) contain post-ganglionic vasodilator and vasoconstrictor fibers that control hindlimb vascular tone. The LSC also contain dorsal root ganglion afferent fibers whose roles in cardiorespiratory status remain poorly understood. The objective of the present study was to characterize the cardiorespiratory responses elicited by electrical stimulation (ES) of a LSC in urethane-anaesthetized male Sprague-Dawley rats (n=6) instrumented to measure/calculate mean arterial blood pressure (MAP), femoral artery blood flow (FBF) and femoral vascular resistance (FVR), brachial artery blood flow (BBF), and brachial vascular resistances (BVR), upper airway pressure (UAP), diaphragmatic EMG, respiratory frequency, inspiratory (iTV) and expiratory (eTV) tidal volumes. The right LSC was identified at the level of L4-L6 and a bipolar electrode was placed for ES (5 Hz, 0.5 msec duration, 0.5 mA amplitude for 10 sec). LSC stimulation caused a distinct pattern of cardiorespiratory responses including (a) a 12% decrease in MAP, (b) 15% decrease in ipsilateral FVR, (c) a 10% decrease in BVR (all measured at the peak decrease in MAP), (d) a 15% increase in iVT, (e) a 10% increase in eVT, (f) a15% increase in respiratory frequency, and (g) a 9% increase in diaphragmatic EMG activity. The result of this study demonstrates that ES of afferent fibers within the LSC elicits an array of cardiorespiratory changes in anesthetized rats that would be consistent with preparing the rats for exercise and for flight.

Use of accelerometer technology for individual tracking of activity patterns, metabolic rates and welfare in farmed gilthead sea bream (Sparus aurata) facing a wide range of stressors

The biosensor technology has the potential to revolutionize the aquaculture industry, but the selection of tagging method, operational mode (stand-alone vs. wireless systems) and telemetry technology ultimately depends on life species, life stage and research question. In particular, AEFishBIT is a small and stand-alone device composed of a tri-axial accelerometer, a microprocessor, a battery and a RFID tag that was designed to be externally attached to the operculum. This unique location serves to provide simultaneous measurements of activity patterns (signals of x- and y-axes) and respiratory frequency (z-axis signal) processed by on-board algorithms. The validity of measurements was initially proved in exercised fish in a swim tunnel respirometer, and its use as a reliable tool for the individual monitoring of whole-organism traits in free-swimming gilthead sea bream was tested herein in fish facing a wide range of biotic and abiotic stressors. The impact of the tagging method, based on the use of monel piercing fish tags with a flexible heat shrink polyethylene ring, was also evaluated and no signs of growth impairment, operculum damage or gill lamellae haemorrhage were found 10 days post-tagging. The autonomy of the device was 6 h of continuous recording with re-programmable lag times and recording schedules of 2 min windows at regular intervals along the experimental period (2–8 days). Such procedure underlined a negative linear correlation between fasting weight loss and operculum breaths, becoming respiratory frequency a reliable indicator of basal metabolic rates. Biosensing signals also highlighted the more continuous physical activity and increased respiratory rates of young fish when comparisons were made between one- and three-year old fish. Also, AEFishBIT measurements evidenced a generalized increase of respiratory frequency during severe hypoxia (2–3 ppm), but the individuals classified as proactive fish also shared an increased physical activity for supporting escape reactions in a milieu with low oxygen availability. Likewise, we also observed an overall increase of physical activity with the decrease of tank space availability, which can contribute to establish stricter criteria of welfare in farmed fish. Finally, the reduction of respiratory frequency was a consistent diagnostic marker of the progression of parasitic enteritis in experimentally infected fish with the myxozoan Enteromyxum leei. Altogether, this work constitutes the proof of concept of the use of biosensor technology as a reliable tool for an individual whole-organism behavioural profiling of farmed fish at laboratory scale, contributing to improve animal welfare and productivity of aquaculture industry.

Cardiorespiratory and hemogasometric effects of epidural ketamine and its associations with morphine and xylazine in sheep

This study aimed to evaluate the cardiorespiratory and hemogasometric effects of epidural ketamine and its associations with morphine and xylazine in ewes submitted to transcervical cervix transposition with a hegar dilator. Ten Santa Inês breed ewes were studied in a cross over model study where three epidural protocols (GK = ketamine 2.0 mg kg-1; GKM = ketamine 2.0 mg kg-1 + morphine 0.1 mg kg-1; GKX = ketamine 2.0 mg kg-1 + xylazine 0.05 mg kg-1) were compared among each other and with a control treatment (GS= saline 1 mL/7.5 kg). The assessed variables were heart rate, respiratory frequency, ear temperature, non-invasive blood pressure and hemogasometric analysis. All parameters were assessed at baseline and then ewes were sedated with an association of acepromazine (0.1 mg kg -1) and diazepam (0.2 mg kg -1). Ten minutes after sedation all parameters were reassessed and afterwards the epidural injections were performed. Hemogasometry was repeated at 15 and 30 minutes after epidural and the other parameters assessed at 05, 15, 30, 45 and 60 minutes after epidural. GKX showed a slight respiratory depression with lower levels of PO2 and a compensatory increase in respiratory frequency. GKM presented the lower temperature mean. All protocols showed few cardiorespiratory effects when compared with control. Epidural with 2.0 mg kg-1 ketamine isolated was considered the best option for short procedures as obstetric manipulations in sheep due to its cardiorespiratory stability when compared with the protocols using associations.

Lesion of Serotonergic Afferents to the Retrotrapezoid Nucleus Impairs the Tachypneic Response to Hypercapnia in Unanesthetized Animals

Hypercapnia promotes an increase in pulmonary ventilation due to the stimulation of brainstem chemosensory cells that are connected to the respiratory network. Among these cells are the raphe serotonergic neurons which widely send projections to distinct central respiratory compartments. Nevertheless, the physiological role of specific raphe serotonergic projections to other chemosensitive sites on the emergence of hypercapnia ventilatory response in vivo still remains to be elucidated. Here we investigated whether the ventilatory response to hypercapnia requires serotonergic inputs to the chemosensitive cells of the retrotrapezoid nucleus (RTN) in the ventrolateral medulla. To test this, pulmonary ventilation was evaluated under baseline conditions and during hypercapnia (7% CO2) in unanesthetized juvenile Holtzman rats (60–90 g) that received bilateral microinjections of either vehicle (control) or anti-SERT-SAP (0.1 mM, 10 pmol/100 nl) toxin in the RTN to retrogradely destroy serotonergic afferents to this region. Fifteen days after microinjections, baseline ventilation was not different between anti-SERT-SAP (n = 8) and control animals (n = 9). In contrast, the ablation of RTN-projecting serotonergic neurons markedly attenuated the hypercapnia-induced increase in respiratory frequency which was correlated with reduced numbers of serotonergic neurons in the raphe obscurus and magnus, but not in the raphe pallidus. The increase in tidal volume during hypercapnia was not significantly affected by anti-SERT-SAP microinjections in the RTN. Our data indicate that serotoninergic neurons that send projections to the RTN region are required for the processing of ventilatory reflex response during exposure to high CO2 in unanesthetized conditions.

Efeitos da ofuroterapia no relaxamento e ganho de peso em recém-nascidos prematuros na unidade de cuidados neonatal

INTRODUÇÃO: Os métodos de banho humanizado são os mais indicados na assistência de recém-nascidos pré-termos (RNPT’s) de baixo peso, por proporcionar a estes uma melhor resposta adaptativa ao ambiente extrauterino, contribuindo para melhora na organização dos sistemas comportamentais, motores e fisiológicos, assim como no desenvolvimento saudável dessa população, através do relaxamento decorrente da imersão do corpo em água morna, evitando assim o gasto energético. OBJETIVO: Investigar os efeitos da ofuroterapia no relaxamento e ganho de peso de RNPT’s, clinicamente estáveis, admitidos em uma Unidade de Cuidados Intermediários Neonatais (UCIN). MÉTODO: Trata-se de um estudo quantitativo, de caráter descritivo e quase exploratório, com uma amostra de 10 recém-nascidos admitidos na UCIN Canguru, do Hospital Maternidade Almeida Castro, Mossoró/RN, Brasil. A população estudada, de baixo peso, foi submetida a 2 sessões semanais de aplicação do método, por 10 minutos em dias alternados. RESULTADOS: Não houve diferença significativa estatisticamente no ganho de peso (p=0,127). Nas variáveis hemodinâmicas, a população estudada apresentou aumento na frequência respiratória (FR) no dia 2 (p=0,028), e diminuição da temperatura corporal no dia 1 (p=0,014) e no dia 2 (p=0,005). Em relação a avaliação da dor, não houve diferenças significativas estatisticamente em ambos os dias. CONCLUSÃO: Apesar de ser observado o relaxamento proporcionado à população do estudo através da aplicação do método, não foram obtidos dados significativamente estatísticos que comprovem a relação entre o relaxamento proporcionado pela ofuroterapia e o ganho de peso dos RNPT’s estudados no presente estudo.

Cardiorespiratory capacity in tetra- and paraplegia shortly after injury

In one hundred patients (86 males, 14 females) with relatively recent spinal cord injuries the oxygen supporting system was evaluated during graded arm ergometry. The patients were assigned according to injury level to 5 subgroups with complete, and to 2 additional groups with incomplete injuries. Mean peak oxygen uptake (VO2) was found to be as low as 0.74 l/min in males with complete tetraplegia and 1.9 l/min in patients with conus and cauda lesions. Peak VO2 was closely correlated (r = 0.74) to the injury level. Peak VO2 was also closely correlated to peak minute ventilation (VE) in all groups. In patients with higher injury levels most of the increase in VE during maximal exercise was due to an increase in respiratory frequency (fR). In patients with tetraplegia and high paraplegia, arm cranking revealed deficient sympathetic regulation of cardiovascular functions resulting in hypotension. In both the complete and incomplete tetraplegic patients there was a relatively low peak heart rate (fH). Peak fH and VO2 varied more in patients with incomplete tetraplegia than in those with complete tetraplegia. Peak VO2 in females with mid-level thoracic paraplegia was on the average lower than in males with corresponding injury levels (16 ml/kg/min against 22 ml/kg/min, respectively). Evaluation of cardiorespiratory functions in spinal cord injured patients during high intensity endurance work performed shortly after the injury adds diagnostic and functionally useful information for the design of rehabilitation and should be recommended as clinical routine.

The carotid bodies exercise control over active expiration but not peak performance during high-intensity treadmill running.

The carotid bodies exercise control over active expiration but not peak performance during high-intensity treadmill running.

Thermoregulatory Responses of Heat Acclimatized Buffaloes to Simulated Heat Waves.

Simple SummaryThe simulated heat wave triggered a relevant thermoregulatory response in heat-acclimatized buffaloes. During the simulated heat wave the high respiratory rate and seating rate limited the heat storage and the levels of hyperthermia. Moderate and transient hyperthermia combined with complete recovery of homeothermy during the night prevented changes in blood parameters, except for ion potassium. The high sweating rates seem to have been crucial for the homeothermy’s maintenance. For the first time, early in the morning, adaptive hypothermia was recorded in buffaloes.Climate change is seen as a significant threat to the sustainability of livestock production systems in many parts of the world, particularly in tropical regions. Extreme meteorological events can result in catastrophic production and death of livestock. Heat waves in particular can push vulnerable animals beyond their survival threshold limits. However, there is little information about buffalo responses to sudden changes in the thermal environment, specifically the heat waves. This study aimed to quantify the thermoregulatory and blood biochemical responses of heat-acclimatized buffaloes to a simulated heat wave. The experiment was designed in a climatic chamber with two periods of 4 days each. Twelve heat acclimated buffalo heifers aged 18 months were used. The climatic chamber environment was set as follows: 4-day period (P1) simulating the same weather conditions of a summer in humid tropical climate used as a baseline, with daily cycle with Ta and RH at 27 ± 1 °C and 76% from 0600 h to 1900 h and 24 ± 1 °C and 80% from 1900 h to 0600 h, and 4-day period (P2), simulating a daily heat wave cycle, from 0600 h to 1900 h with Ta and RH kept at 36 °C and 78% and from 1900 h to 0600 h, 27 °C and 74%. All animals were subject to both treatments and data were analyzed by a repeated measure analysis of variance, with post-hoc pooling comparison performed by Tukey’s test. In P2, there was observed a significant increase in respiratory frequency (p < 0.01), found four times in P1. The sweating rates were quite high in both periods; still, there were significant increases in P2 compared to P1 (p < 0.01) (4931 and 3201 g/m2/h, respectively). A slight but significant increase in rectal temperature was observed during the day (p < 0.01), with a rising until 1900 h. The simulated heat wave in P2 did not affect the values of the erythrogram or leukogram, excluding the significant reduction in K+ (p < 0.05). The low heat storage and the subsequent fast and full recovery of the thermal balance late afternoon appear to be related to the high sweating rate values. The massive sweating rate emphasizes its relevance in the maintenance of buffalo homeothermy. The absence of changes in hematological parameters has revealed the considerable physiological resilience of buffaloes toward simulated heat waves.

Relaxin‐3 receptor (RXFP3) mediated modulation of central respiratory activity

The neuropeptide, relaxin‐3, is expressed by pontine nucleus incertus (NI) neurons. Relaxin‐3 and synthetic agonist peptides modulate arousal and cognitive processes via activation of the rela xin‐ family peptide 3 receptor (RXFP3). We recently demonstrated that a double‐chain RXFP3 peptidomimetic (RXFP3‐A2) in the nucleus of the solitary tract (NTS) triggered a mild stimulation of respiration and augmented the chemoreceptor reflex in an in situ perfused brainstem preparation ( Furuya et al., 2020). In the present study, we assessed the central respiratory effects of systemic application and local microinjection into the NTS, Kölliker‐Fuse nucleus (KF) or NI of a single chain RXFP3 peptidomimetic (B18) in the perfused brainstem preparation.Systemic application of B18 (2 μM) triggered a dose‐dependent increase in respiratory rate by 22 ± 8%. At this concentration of B18, the NaCN‐evoked (0.1% w/v, 100 μl, bolus injection) tachycardia of the arterial chemoreceptor reflex was augmented by 95 ± 14% compared to control (p&lt;0.001, n=4). Local microinjections into the NTS also increased respiratory frequency (28 ± 5%, p&lt;0.05, n=6) and enhanced the NaCN‐evoked tachycardia by 59%. Microinjections into the KF only triggered a mild increase in respiratory frequency (18 ± 7%, p&lt;0.05, n=6) but had no effect on the NaCN‐evoked chemoreceptor reflex. Finally, microinjections into the NI (n=6) had no effect on either stationary breathing activity, or on the chemoreceptor reflex. We conclude that relaxin‐3 neurons target RXFP3 in respiratory control areas and acts as a general respiratory stimulant, causing mild increases in respiratory frequency. Importantly, RXFP3 stimulation significantly enhanced the respiratory response of arterial chemoreceptor reflex, implicating a major neuromodulatory role in this specific reflex pathway.

Orexin Neurons Contribute to Central Modulation of Respiratory Drive by Progestins on ex vivo Newborn Rodent Preparations.

Dysfunction of central respiratory CO2/H+ chemosensitivity is a pivotal factor that elicits deep hypoventilation in patients suffering from central hypoventilation syndromes. No pharmacological treatment is currently available. The progestin desogestrel has been suggested to allow recovery of respiratory response to CO2/H+ in patients suffering from central hypoventilation, but except the fact that supramedullary regions may be involved, mechanisms are still unknown. Here, we tested in neonates whether orexin systems contribute to desogestrel’s central effects on respiratory function. Using isolated ex vivo central nervous system preparations from newborn rats, we show orexin and almorexant, an antagonist of orexin receptors, supressed strengthening of the increase in respiratory frequency induced by prolonged metabolic acidosis under exposure to etonogestrel, the active metabolite of desogestrel. In parallel, almorexant suppressed the increase and enhanced increase in c-fos expression in respiratory-related brainstem structures induced by etonogestrel. These results suggest orexin signalisation is a key component of acidosis reinforcement of respiratory drive by etonogestrel in neonates. Although stage of development used is different as that for progestin clinical observations, presents results provide clues about conditions under which desogestrel or etonogestrel may enhance ventilation in patients suffering from central hypoventilation syndromes.

Kömür madeni ortamında tutulan sıçanlarda akciğer toksisitesinin in vivo solunum kayıtları ile değerlendirilmesi: Deneysel Bir Çalışma

OBJECTIVE: Mine workers exposed to dusts or toxic gasses in occupational atmospheric conditions. Pneumoconiosis and other lung diseases are charecterized by the pathogenesis of coal dust-caused pulmonary toxicity associated with reactive oxygen species (ROS). MATERIALS AND METHODS: This study was conducted to investigate the respiration failures and fibrosis in rats after being exposed to coal dust and gases in mine atmosphere. Another aim was to study the therapeutic effect of erdosteine as antioxidant therapy. Rats were exposed to mine ambience for four week, and then they were breathed in the clean air for four week. The respiratory functions of rats were recorded once a week for eight week, as in vivo. The fibrosis of lung tissue levels, the oxidant/antioxidant status, and cytokines of inflammation in bronchoalveolar lavage fluids (BALFs) were evaluated, at the end of the processes.RESULTS: We observed to be the beginning of respiratory abnormalities in animals exposed to coal dust in second week. The end of fourth week, there were the increase of respiratory frequency and along with the decrease of respiratory depth. The respiratory failures were not improved in clean ambience, moreover apnea were appearance in the end of six week (the second week of clean air). Deaths were 28% in animals. Erdosteine administer to rats could not fully abolished to the pulmonary toxicity, however could able to hold to toxicity, and also there were not dies in rats administered to erdosteine. Coal dust exposure was resulted in fibrosis with higher hydroxyproline (HP) levels, cytokine inflammation with higher interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels, and lipid peroxidation with an increased malondialdehyde (MDA) levels, according to the healthy. A dramatically run out of endogen antidote sulfide pools (GSH), and an increased MPO activity were dedected in the mine dusts and gasses exposure group, according to the healthy animals. High biochemical index of toxicity were partly balanced by erdosteine. CONCLUSIONS: Our experimental findings support the hypothesis that ROS is induced coal workers' pneumoconiosis. Re-oxygenation cannot be getting it together to reverse the pulmonary toxicity. On the top of it, it can make its pathogenesis further exaggerating and even worse. On this account we heartily speculate that re-oxygenation should be by steps in mine workers. In addition the antioxidant therapy may be partly a choice be able to tolerate the coal dust-induced lung toxicity of mine workers.

A Novel Sympathoexcitatory Pathway between The Deep Superior Colliculus and The Rostral Ventromedial Medulla

IntroductionThe superior colliculus plays key roles in the immediate processing of threatening sensory stimuli and generates rapid behavioural responses that are critical for survival. We have previously found that disinhibition of the deep superior colliculus (dSC) unmasks coordinated respiratory, sympathetic and somatomotor outputs that are independent of processing in higher centres. We postulate that these effects are a result of direct innervation of autonomic and respiratory medullary neurons based on the results of neuroanatomical tracing studies that identified dSC synaptic contacts on spinally projecting neurons within the rostral ventromedial medulla (RVMM). In the present study we investigate the physiological significance of this relay and compare effects of dSC stimulation to activation of dSC‐RVMM terminals.MethodsWe used an AAV vector to express Channelrhodopsin2 (ChR2) in the dSC and chronically implanted a fibre optic cannula into the dSC. After transgene expression electrophysiology experiments were conducted under urethane anesthesia with rats instrumented to record blood pressure, diaphragmatic EMG and splanchnic sympathetic nerve activity (SNA). One subset of experiments then positioned the optrode in the RVMM to deliver light to the terminal projections from the dSC. For the other subset of experiments, extracellular recordings were made of spinally projecting RVMM neurons.ResultsdSC photoactivation evoked an increase in respiratory frequency (35±8.7%, P=&lt;0.01, N=7) and heart rate (11±2.6 bpm, P=&lt;0.01, N=7), and a modest change in blood pressure when compared to controls. Stimulus‐triggered averaging of SNA revealed short‐latency excitatory potentials in most cases. Photoactivation of ChR2‐expressing dSC‐RVMM terminals evoked similar effects on cardiorespiratory outputs as dSC stimulation, with an increase in respiratory frequency (14 ±9.2%, P&lt;0.001, N=6) and blood pressure (13 ±2 mmHg P&lt;0.01, N=7), as well as qualitatively similar sympathoexcitation. In preliminary experiments that recorded extracellular action potentials in bulbospinal RVMM neurons we recorded excitatory effects of dSC stimulation in 6/8 spontaneously active neurons.ConclusionWe conclude that optogenetic activation of dSC neurons that project to the RVMM can drive cardiorespiratory effects that are consistent with our previous findings and that dSC stimulation evokes excitatory effects in some RVMM bulbospinal neurons. This confirms our hypothesis of the existence of a previously uncharacterized excitatory pathway between the dSC and RVMM. Ongoing experiments will functionally characterize RVMM neurons that receive dSC input.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Activation of Phox2b-Expressing Neurons in the Nucleus Tractus Solitarii Drives Breathing in Mice.

The nucleus tractus solitarii (NTS) is implicated in the control of breathing, but the neuronal phenotype and circuit mechanism involved in such a physiological function remain incompletely understood. This study focused on the respiratory role of paired-like homeobox 2b gene (Phox2b)-expressing NTS neurons and sought to determine whether selective stimulation of this set of neurons activates breathing in male mice. A Cre-dependent vector encoding a Gq-coupled human M3 muscarinic receptor (hM3Dq) was microinjected into the NTS of Phox2b-Cre transgenic mice. The hM3Dq-transduced neurons were pharmacologically activated in conscious mice while respiratory effects were measured by plethysmography. We demonstrate that chemogenetic stimulation of Phox2b-expressing NTS neurons significantly increased baseline minute volume via an increase in respiratory frequency rather than tidal volume. Chemogenetic stimulation also synergized with moderate CO2 stimulation to enhance pulmonary ventilatory response. Selective ablation of Phox2b-expressing NTS neurons notably attenuated a hypercapnic ventilatory response. Moreover, histological evidence revealed that stimulation of Phox2b-expressing NTS neurons increased neuronal activity of the preBötzinger complex. Finally, we presented the neuroanatomical evidence of direct projection of Phox2b-expressing NTS neurons to putative respiratory central pattern generator. Overall, these findings suggest that selective activation of Phox2b-expressing NTS neurons potentiates baseline pulmonary ventilation via an excitatory drive to respiratory central pattern generator and this group of neurons is also required for the hypercapnic ventilatory response.SIGNIFICANCE STATEMENT The nucleus tractus solitarii (NTS) has been implicated in the control of breathing. The paired-like homeobox 2b gene (Phox2b) is the disease-defining gene for congenital central hypoventilation syndrome and is restrictively present in brainstem nucleus, including the NTS. Using a chemogenetic approach, we demonstrate herein that selective stimulation of Phox2b-expressing NTS neurons vigorously potentiates baseline pulmonary ventilation via an excitatory drive to respiratory central pattern generator in rodents. Genetic ablation of these neurons attenuates the hypercapnic ventilatory response. We also suggest that a fraction of Phox2b-expressing neurons exhibit CO2 sensitivity and presumably function as central respiratory chemoreceptors. The methodology is expected to provide a future applicability to the patients with sleep-related hypoventilation or apnea.